ABSTRACT
BACKGROUND@#Degeneration of the annulus fibrosus (AF), an important structure of the intervertebral disc, is one of the main causes of degenerative disc disease. Fabrication of scaffolds replicating the stratified microstructure of the AF is critical for the successful regeneration of AF. @*METHODS@#In this study, we cultured rabbit AF-derived stem cells (AFSCs) using fabricated electrospun fibrous poly-Llactic acid scaffolds with different diameters. We applied cyclic tensile strain (CTS) on the scaffolds to regulate the differentiation of AFSCs into specific cell types that resided at the inner, middle, and outer zones of the AF. @*RESULTS@#We found that the morphologies of AFSCs on the smaller-fiber-diameter scaffolds were nearly round, whereas spindle-like cells morphologies were observed on large-diameter scaffolds. CTS enhanced these phenomena and made the cells slender. The expression levels of collagen-I in cells increased as a function of the fiber diameter, whereas collagen-II and aggrecan exhibited opposite trends. Moreover, the application of CTS upregulated the gene expressions of collagen-I, collagen-II, and aggrecan. @*CONCLUSION@#Overlaying the scaffolds with different CTS-stimulated cells could eventually lead to engineered AF tissues with hierarchical structures that approximated the native AF tissue. Thus, the proposed methodologies could be potentially applied for AF regeneration.
ABSTRACT
BACKGROUND@#Degeneration of the annulus fibrosus (AF), an important structure of the intervertebral disc, is one of the main causes of degenerative disc disease. Fabrication of scaffolds replicating the stratified microstructure of the AF is critical for the successful regeneration of AF. @*METHODS@#In this study, we cultured rabbit AF-derived stem cells (AFSCs) using fabricated electrospun fibrous poly-Llactic acid scaffolds with different diameters. We applied cyclic tensile strain (CTS) on the scaffolds to regulate the differentiation of AFSCs into specific cell types that resided at the inner, middle, and outer zones of the AF. @*RESULTS@#We found that the morphologies of AFSCs on the smaller-fiber-diameter scaffolds were nearly round, whereas spindle-like cells morphologies were observed on large-diameter scaffolds. CTS enhanced these phenomena and made the cells slender. The expression levels of collagen-I in cells increased as a function of the fiber diameter, whereas collagen-II and aggrecan exhibited opposite trends. Moreover, the application of CTS upregulated the gene expressions of collagen-I, collagen-II, and aggrecan. @*CONCLUSION@#Overlaying the scaffolds with different CTS-stimulated cells could eventually lead to engineered AF tissues with hierarchical structures that approximated the native AF tissue. Thus, the proposed methodologies could be potentially applied for AF regeneration.
ABSTRACT
Degenerative disc disease (DDD) is a leading cause of low back pain, which severely affects the quality of life and incurs significant medical cost. Annulus fibrosus(AF) injuries can lead to substantial deterioration of intervertebral disc degeneration. However, the AF repair/regeneration remains a challenge due to the intrinsic cellular, biochemical and biomechanical heterogeneity of AF tissue. Tissue engineering would be a promising approach for AF regeneration. This article aims to provide a brief overview of the fundamental aspects of AF, the current achievements and future challenges of AF tissue engineering. A multidisciplinary approach is proposed for future studies to fully mimic the native AF tissue and its microenvironment, including choosing adequate cell source, preparing scaffolds with hierarchical microstructures, supplementing appropriate growth factors, and enforcing suitable mechanical stimulation. Hopefully, the engineered AF tissues would be effectively used to facilitate the treatment of DDD in the future.